Our understanding of the pathogenesis of AIDS has advanced considerably since the disease was first reported 15 years ago. We now know that the primary damage inflicted by HIV-1 is mainly brought about by active virus replication. With the advent of sensitive tools for monitoring HIV replication in vivo, an individual's risk of disease progression can be assessed early in the course of the infection and the efficacy of antiviral therapies can now be determined accurately and expeditiously. When used appropriately, potent combinations of antiviral drugs seem to be able to circumvent the inherent tendency of HIV-1 to generate drug-resistant viruses, the main reason for failure of all antiviral therapies, and are significantly more effective than earlier approaches. For the first time, rational approaches to contain and perhaps eliminate HIV-1 infection can be pursued.